title: [Molecular basis of Hirschsprung disease].
abstract: Hirschsprung disease (HSCR) is a congenital malformation caused by the absence of ganglion cells in the myenteric and submucosal plexuses of the gut. Recent studies have shown that mutations in the RET, glial-cell-derived neurotrophic factor (GDNF), endothelin-B receptor (EDNRB), endothelin-3 genes are responsible for the occurrence of aganglionosis. Those genes are involved in the development of neural crest derivatives. The RET gene mutation are found in 50% of familial cases and 15% of sporadic cases. The mutations in other genes were found under 10%. In addition to such a low detection rate of the mutations, incomplete penetrance of the mutation was found in all four genes. Those results support multifactorial or polygenic feature of Hirschsprung disease. The additional candidate genes responsible for this disease will be identified along the signaling pathway through RET and EDNRB.
authors.affiliation: Department of Pediatric Surgery, Osaka University Medical School.
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: A
authors.initials: A
authors.lastname: Okada
mesh_terms: D000818:Animals; D029721:Drosophila Proteins; D019334:Endothelin-3 / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D019334:Endothelin-3; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D019009:Proto-Oncogene Proteins c-kit; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila